β-ラクタム系抗生物質の薬学的研究(第6報)6-[D(-)-α-(4-Ethyl-2,3-dioxo-1-piperazinecarboxamido)phenylacetamido]penicillanic Acid(T-1220)の代謝について

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Metabolism of 6-[D (-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido) phenylacetamido] penicillanic acid (T-1220), a new β-lactam antibiotic, was studied in vivo and in vitro. Only unchanged T-1220 was detected by bioautography in urine of human, monkeys, dogs, rats, and mice receiving T-1220 intramuscularly. When ^<14>C-labeled T-1220 was administered to rats, most of the radioactive product was excreted unchanged in the urine, but two metabolites were detected in a minute amount by autoradiography. These metabolites were identified as ^<14>C-labeled α-{3-[2-(N-ethyl-N-oxaloamino) ethyl] ureido}-benzylpenicillin (^<14>C-T-1220A) and ^<14>C-labeled α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido) benzylpenicilloic acid (^<14>C-T-1220B) by thin-layer chromatography, electrophoresis, and high-pressure liquid chromatography. Metabolism of ^<14>C-T-1220 and its mechanism were studied by using high-pressure liquid chromatography for the separation and radioactive measurement for the determination. In the case of the intramuscular administration of ^<14>C-T-1220 to rats, about 92% of the radioactivity was excreted unchanged in urine and bile, but about 94% of the radioactivity in the feces was ^<14>C-T-1220B. The same results were found in rats pretreated with SKF-525A and phenobarbital. In situ studies showed that ^<14>C-T-1220 changed to ^<14>C-T-1220B in the intestinal tracts, and in vitro studies showed that ^<14>C-T-1220 changed to ^<14>C-T-1220B in fecal homogenate. From these results, it seemed that ^<14>C-T-1220 was changed to ^<14>C-T-1220B by β-lactamase produced from intestinal flora.
社団法人日本薬学会の論文
1977-10-25

β-ラクタム系抗生物質の薬学的研究(第6報)6-[D(-)-α-(4-Ethyl-2,3-dioxo-1-piperazinecarboxamido)phenylacetamido]penicillanic Acid(T-1220)の代謝について

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